Clinical Studies with Broadly Neutralizing Antibodies Michel C. Nussenzweig AIDS is a preventable disease. Nevertheless, according to UNAIDS, 2.1 million of individuals were infected with HIV-1 in 2015 worldwide. An effective vaccine is highly desirable. Most vaccines in clinical use today prevent infection because they elicit antibodies that block pathogen entry. Consistent with this general rule, studies in experimental animals have shown that broadly neutralizing antibodies to HIV-1 can prevent infection, suggesting that a vaccine that elicits such antibodies would be protective. However, despite significant efforts over the last 30 years, attempts to elicit broadly HIV-1 neutralizing antibodies by vaccination failed until recent experiments in genetically engineered mice were finally successful. Nevertheless, a small fraction of HIV-1-infected individuals develop antibodies that effectively neutralize the majority of existing HIV-1 isolates. Single cell antibody cloning methods revealed that this serum neutralizing activity is due to one or a combination of monoclonal antibodies that target different non-overlapping epitopes on the HIV-1 envelope spike. When passively transferred, many of these newly discovered antibodies protect against infection in humanized mice and macaques, even when present at very low concentrations. In addition, combinations of antibodies targeting non-overlapping epitopes can control active infection in humanized mice and macaques. Finally, when they are administered together with agents that induce viral transcription to activate latently infected cells, antibodies decrease the incidence of viral rebound from the latent reservoir in HIV-1-infected humanized mice. These preclinical findings have been extended to humans in phase 1 clinical trials of 2 antibodies that target non-overlapping epitopes 3BNC117 and 10-1074. The results of those trials will be discussed.
CROI Conference
